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ABSTRACT A 3-year histological study of disease prevalence in 657 blue crabs, Callinectes sapidus, dredged from 31 sites within Maryland portions of Chesapeake Bay during autumn and winter revealed the presence of many diverse parasites and symbionts. A large number of crabs exhibited hemocytic infiltration and encapsulation. Parasites and symbionts identified included viruses (Baculo-B and RLV-RhVA), a rickettsia-like microorganism (RLM), an unusual strandlike organism, unidentified microsporidians and gregarines, both parasitic (Mesanophrys chesapeakensis) and symbiotic (Lagenophrys callinectes and Epistylis sp.) cilates, the nemertean Carcinonemertes carcinophila, and trematode metacercariae, some hyperparasitized by the haplosporidian Urosporidium crescens. Significant differences in disease and parasite frequencies were observed among survey periods. The prevalence of some tissue responses and parasites exhibited seasonal patterns of infection and infestation.